OBJECTIVETo study the alteration of circulating microRNAs in 4-(methylnitrosamino)-1-(3-pyridyl) -1-butanone (NNK)-induced early stage lung carcinogenesis.

METHODSA lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 1, 5, 10, and 20 following NNK treatment.

RESULTSNo lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment.

CONCLUSIONThe expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.

Adenocarcinoma ; chemically induced ; Animals ; Carcinogenesis ; Cell Line, Tumor ; Gene Expression Regulation ; physiology ; Humans ; Lung ; drug effects ; pathology ; Lung Neoplasms ; blood ; chemically induced ; metabolism ; Male ; MicroRNAs ; blood ; genetics ; metabolism ; Nitrosamines ; pharmacology ; Rats ; Rats, Inbred F344

Adenocarcinoma ; pathology ; Animals ; Carcinoma, Squamous Cell ; chemically induced ; pathology ; Cell Line, Tumor ; Dimethylnitrosamine ; analogs & derivatives ; Disease Models, Animal ; Esophageal Neoplasms ; chemically induced ; pathology ; Humans ; Neoplasm Transplantation

OBJECTIVETo observe the gene expression of herpes simplex virus type 1 thymidine kinase (HSVl-tk) in rat malignant ovarian tumor tissues and the therapeutic effect of ganciclovior (GCV) after intra-arterial infusion of HSVl-tk gene therapy mediated by GE7-delivery system.

METHODSA GE7-polylysine/pCMV-HSV1-tk/polylysine-HA20 4-element complex was constructed. Eighteen rats with DMBA-induced ovarian tumor were divided into 3 groups as Atk, ANS and Vtk groups. The 4-element complex GE7-polylysine/pCMV-HSV1-tk/polylysine-HA20 was injected via the ovarian artery into the rats of Atk group, saline buffer was injected in the ANS groups, and the 4-element complex was injected via the tail vein into the rats of Vtk group. All rats received intraperitoneal injection of GCV in a dose of 50 mg/kg daily for 10 days. The rats were sacrificed 3 days after the final dose of GCV, and the tumor weight was measured and tumor growth inhibition rate was calculated. Flow cytometry was used to assess the cell cycle and apoptosis.

RESULTSThe tumor weight in the rats of Atk group was (4.77 ± 2.31) g, significantly lower than that of ANS group [(14.66 ± 6.26) g, P < 0.01] and Vtk group [(17.53 ± 7.19) g, P < 0.01]. The tumor growth inhibition rate of the Atk group was 67.5%, while that of Vtk group was -19.6%. The flow cytometry showed that S-phase tumor cells in the Atk group were (54.32 ± 9.65)%, significantly higher than that in the ANS (27.43 ± 9.22)% and (30.16 ± 11.57)% in the Vtk group (both P < 0.01). The tumor cell apoptosis rate in the Atk group was (39.15 ± 12.16)%, significantly higher than that in the ANS group [(11.86 ± 5.28)%, P < 0.01] and Vtk group [(14.32 ± 6.43)%, P < 0.01].

CONCLUSIONHSV1-tk/GCV gene therapy system mediated by GE7 non-viral delivery system via ovarian arterial infusion effectively causes cell cycle arrest at S phase and enhances cell apoptosis, therefore, exerts an inhibitory effect on tumor growth.

9,10-Dimethyl-1,2-benzanthracene ; Adenocarcinoma ; chemically induced ; pathology ; therapy ; Animals ; Antiviral Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Female ; Ganciclovir ; pharmacology ; Gene Transfer Techniques ; Genetic Therapy ; Herpesvirus 1, Human ; genetics ; metabolism ; Infusions, Intra-Arterial ; Ovarian Neoplasms ; chemically induced ; pathology ; therapy ; Random Allocation ; Rats ; Rats, Wistar ; Thymidine Kinase ; genetics ; metabolism

OBJECTIVETo investigate the relationship between serum concentration of fluorouracil and therapeutic efficacy as well as adverse reactions in patients with unresectable locally advanced or measurable metastatic colorectal cancer, and to analyze its role in further improving therapeutic efficacy and reducing adverse reactions of fluorouracil-based chemotherapy.

METHODSEighty-six patients were randomly assigned into three groups according to the average plasma concentration of fluorouracil after three cycles of chemotherapy with the initial regimen of two weeks FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil) or FOLFIRI (irinotecan + leucovorin + fluorouracil): group 1 (plasma concentration of fluorouracil < 25 ng/ml), group 2 (25 - 35 ng/ml) and group 3 (> 35 ng/ml). The blood samples were taken at 12 h after continuous infusion of fluorouracil in each cycle and the plasma concentration of fluorouracil was detected by high performance liquid chromatography (HPLC) (about 5 am ± 1 h). The relationship between the drug plasma concentration, therapeutic efficacy and adverse reactions in different fluorouracil plasma concentration arms was analyzed retrospectively.

RESULTSThe average plasma concentrations of fluorouracil of the three groups were (23.48 ± 1.95) ng/ml, (31.47 ± 2.33) ng/ml and (39.89 ± 3.87) ng/ml, respectively (P < 0.01). As for therapeutic efficacy, the median OS of the groups 2 and 3 were 18.0 and 17.5 months, significantly higher than that in the group 1 (13.0 months, P < 0.01). The PFS were 4.5, 7.5 and 8.0 months, respectively (P < 0.01). In terms of adverse reactions, the incidences of bone marrow suppression, mucositis and diarrhea in the group 3 were significantly higher than that in the first two groups (P = 0.02, P = 0.04 and P = 0.02).

CONCLUSIONSThe patients with local advanced and metastatic colorectal cancer, receiving fluorouracil-based chemotherapy, and with an average plasma concentration of fluorouracil between 25 - 35 mg/L have a better prognosis, and lower incidence of adverse reactions such as bone marrow suppression, mucositis and diarrhea.

Adenocarcinoma ; blood ; drug therapy ; pathology ; Adenocarcinoma, Mucinous ; blood ; drug therapy ; pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bone Marrow Diseases ; chemically induced ; Colonic Neoplasms ; blood ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Female ; Fluorouracil ; adverse effects ; blood ; pharmacokinetics ; therapeutic use ; Humans ; Leucovorin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Mucositis ; chemically induced ; Neoplasm Staging ; Organoplatinum Compounds ; adverse effects ; therapeutic use ; Random Allocation ; Rectal Neoplasms ; blood ; drug therapy ; pathology ; Remission Induction ; Survival Rate

OBJECTIVETo evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma.

METHODSTwo hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed.

RESULTSTwo hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different.

CONCLUSIONSOral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.

Adenocarcinoma ; drug therapy ; pathology ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Drug Combinations ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Male ; Middle Aged ; Neoplasm Staging ; Oxonic Acid ; administration & dosage ; adverse effects ; Paclitaxel ; administration & dosage ; adverse effects ; Prospective Studies ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; Survival Rate ; Tegafur ; administration & dosage ; adverse effects

OBJECTIVEThe combination of oxaliplatin and S-1 is effective in patients with advanced gastric cancer. The purpose of this study was to analyze the safety and compliance of this combination regimen as adjuvant chemotherapy in patients with gastric cancer.

METHODSClinical data of 71 patients with gastric cancer treated with oxaliplatin plus S-1 as adjuvant chemotherapy in the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) from Jan 1(st), 2010 to Jan 1(st), 2012 were retrospectively reviewed. The types and incidence rate of adverse events related to chemotherapy and the results of follow up of the patients were analyzed.

RESULTSAmong the 71 cases, 17 were treated with oxaliplatin biweekly, while 54 with oxaliplatin triweekly. The most common adverse events were neutropenia (n = 49, 69.0%), nausea/vomiting (n = 51, 71.8%), and anorexia (n = 49, 69.0%). The most frequent grade 3-4 toxicities were neutropenia (n = 13, 18.3%), thrombocytopenia (n = 10, 14.1%), anorexia (n = 5, 7.0%) and nausea/vomiting (n = 4, 5.6%). Seven (87.5%) of the 8 patients previously treated with neoadjuvant chemotherapy experienced thrombocytopenia in the postoperative adjuvant chemotherapy, and four (50%) of the 8 patients experienced grade 3-4 thrombocytopenia. The rates of grade 3-4 adverse events in patients aged 65-years or older were similar to that in younger patients.

CONCLUSIONSThe combination of oxaliplatin and S-1 used as adjuvant chemotherapy is well tolerated by patients with gastric cancer. Neutropenia, thrombocytopenia, nausea/vomiting and anorexia are the major treatment-related adverse events. Patients who received neoadjuvant chemotherapy do not well tolerate this regimen as postoperative adjuvant chemotherapy. This combination regimen has a manageable tolerability profile in adjuvant setting in patients ≥ 65 years old.

Adenocarcinoma ; drug therapy ; pathology ; surgery ; Adult ; Aged ; Anorexia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Chemotherapy, Adjuvant ; Drug Combinations ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoadjuvant Therapy ; Neoplasm Staging ; Neutropenia ; chemically induced ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Oxonic Acid ; administration & dosage ; adverse effects ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; pathology ; surgery ; Survival Rate ; Tegafur ; administration & dosage ; adverse effects ; Thrombocytopenia ; chemically induced

OBJECTIVETo evaluate the efficacy of short-term intermittent prophylactic use of a recombinant human thrombopoietin (rhTPO) in chemotherapy-induced severe thrombocytopenia in lung cancer patients.

METHODS24 advanced non-small cell lung cancer (NSCLC) patients who experienced severe thrombocytopenia in the last chemotherapy cycle received prophylactic rhTPO treatment in the next chemotherapy cycle (prophylactic treated cycle, PTC). rhTPO was given subcutaneously 300 U×kg(-1)×d(-1) on days 2, 4, 6, and 9 after the initiation of chemotherapy. Platelet count was monitored and compared with that in the previous treatment cycle (control cycle, CC).

RESULTSThe lowest platelet count in the prophylactic rhTPO cycle was significantly higher than that in control cycle [(56 ± 16) × 10(9)/L vs. (28 ± 13) × 10(9)/L, P < 0.001]. The duration of thrombocytopenia was also shortened by the prophylactic rhTPO [(8 ± 2) d vs. (12 ± 3) d, P < 0.001]. The area under curve (AUC) of platelet count (21 days) was significantly increased [(3517 ± 685) × 10(9)/L vs. (2063 ± 436) × 10(9)/L, P < 0.001]. The time to platelet nadir and peak was not affected.

CONCLUSIONProphylactic use of rhTPO can attenuate the severity and shorten the duration of chemotherapy-induced thrombocytopenia in lung cancer patients.

Adenocarcinoma ; blood ; drug therapy ; pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Area Under Curve ; Carboplatin ; administration & dosage ; adverse effects ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Dizziness ; chemically induced ; Female ; Fever ; chemically induced ; Humans ; Lung Neoplasms ; blood ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Platelet Count ; Recombinant Proteins ; adverse effects ; therapeutic use ; Thrombocytopenia ; blood ; chemically induced ; drug therapy ; Thrombopoietin ; adverse effects ; therapeutic use

OBJECTIVETo evaluate the efficacy and toxicity of paclitaxel with low-dose cisplatin and 5-fluorouracil continuous infusion in the treatment of advanced gastric carcinoma.

METHODSThe patients were treated with paclitaxel liposome 60 mg/m(2) i.v. gtt on d1, 8, 15, DDP 15 mg×m(-2)×d(-1) by i.v. gtt on d1-5, 5-Fu 500 mg×m(-2)×d(-1) by civ for 120 h, administered every 21 days.

RESULTSOut of the whole group, 3 cases achieved CR, 29 cases achieved PR with an ORR of 54.2% and median TTP of 7.1 months. Out of 40 cases in the primary treatment, 3 cases achieved CR, 22 cases achieved PR with an ORR of 62.5% and median TTP of 7.6 months. Out of 20 evaluable retreated cases, no case achieved CR, 7 cases achieved PR with an ORR of 36.8% and median TTP 6.3 months. The main toxicities were hematological toxicities, nausea and vomiting of grade I-II.

CONCLUSIONThe combination regimen of paclitaxel, low-dose cisplatin and 5-fluorouracil is effective and well tolerated for patients with advanced gastric carcinoma, especially for primary treatment cases. It is worthy of further study.

Adenocarcinoma ; drug therapy ; pathology ; secondary ; surgery ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; therapeutic use ; Cisplatin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Leukopenia ; chemically induced ; Liposomes ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; adverse effects ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; surgery ; Survival Rate ; Vomiting ; chemically induced ; Young Adult

OBJECTIVETo observe and compare the response rate and toxicity of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer.

METHODSSixty-three patients with advanced gastric cancer were randomly divided into two groups. The CPT-11 + CAP group consisted of 32 patients who received irinotecan plus capecitabine: CPT-11 100 mg/m(2) was injected in 90 minutes on d 1, 8;capecitabine 2000 mg/m(2), bid, with the first dose in the evening of day 1 and last dose the morning of day 15, repeated for every 21 days. The L-OHP + CAP group consisted of 31 patients who received oxaliplatin plus capecitabine: oxaliplatin 100 mg/m(2) on day 1, capecitabine 2000 mg/m(2), bid, with the first dose in the evening of day 1 and last dose the morning of day 15, repeated for every 21 days. Two or more cycle chemotherapy was completed in each group.

RESULTSIn the CPT-11 + CAP group, no patient achieved complete response and 13 patients achieved partia1 response. The overall response rate was 40.6% (13/32), and the median progression-free survival time was 6.3 months. In the L-OHP + CAP group, no patient achieved complete response and 12 patients achieved partial response. The overall response rate was 38.7% (12/31), and the median progression-free survival time was 6.1 months. There was no significant difference between them (P > 0.05). The most common toxicities were gastrointestinal reaction, peripheral neuropathy and myelosuppression in the two groups. Patients in CPT-11 + CAP group experienced more III/IV diarrhea (28.1%/3.2%, P = 0.018). On the contrary, the rate of III/IV neurotoxicity in the group B was higher (25.8%/3.1%, P = 0.027). No chemotherapy-related death occurred.

CONCLUSIONThe therapeutic effects of irinotecan or oxaliplatin combined with capecitabine in the treatment of advanced gastric cancer are good and comparable, and their toxicities are tolerable.

Adenocarcinoma ; drug therapy ; pathology ; secondary ; Adult ; Aged ; Agranulocytosis ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Capecitabine ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Diarrhea ; chemically induced ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Neuritis ; chemically induced ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Ovarian Neoplasms ; drug therapy ; secondary ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; Young Adult

OBJECTIVETo investigate the early efficacy of nedaplatin combined with megestrol in concurrent chemoradiotherapy for advanced cervical cancer.

METHODSForty-two cases of cervical cancer (FIGO IIb to IVa) were divided randomly into two groups: radiotherapy alone (21 cases) and radiation plus chemotherapy (Nedaplatin) group. The same radiotherapy was given to the two groups. Patients of the RT + C group received nedaplatin 30 mg/m2 in intravenous drip infusion once weekly on day 1, for 4 to 5 weeks, and megestrol 160 mg orally every day during the radiation therapy.

RESULTSThe early outcome: the complete remission rate was 81.0% and partial remission rate was 19.0% in the RT + C group, significantly better than the CR (38.1%) and PR (42.9%) in the RT group. The 1-year survival rates in the two groups were 100% (21/21) and 81.0% (17/21), respectively, with a significant difference between the two groups (P<0.05).

CONCLUSIONSThe combination of nedaplatin and megestrol with concurrent chemoradiotherapy can improve the early outcome of advanced cervical cancer, with somewhat increased but tolerable adverse effects.

Adenocarcinoma ; drug therapy ; pathology ; radiotherapy ; Adult ; Alopecia ; chemically induced ; Anemia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Brachytherapy ; Chemoradiotherapy ; adverse effects ; Diarrhea ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Iridium Radioisotopes ; therapeutic use ; Leukopenia ; chemically induced ; Megestrol ; administration & dosage ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Particle Accelerators ; Radiotherapy, High-Energy ; Remission Induction ; Survival Rate ; Thrombocytopenia ; chemically induced ; Uterine Cervical Neoplasms ; drug therapy ; pathology ; radiotherapy